Pathophysiology of thalassaemia

Most of the major clinical manifestations of the beta-thalassaemias can be related to the deleterious effects of imbalanced globin chain synthesis on erythroid maturation and red cell survival. The destruction of red cell pro genitors and their progeny results from an extremely complex series of mech anisms all related to the presence of excess alpha-globin chain production. These include mechanical damage, interference with cell division and oxida tive destruction of both organelles and components of the red cell membrane . The unequal distribution of gamma-globin chains between different precurs ors, and the intense selection of those with relatively higher levels of ga mma chain production, lead to an extremely heterogeneous cell population in the peripheral blood. Iron overload, due to increased gastrointestinal abs orption and blood transfusion is the major cause of tissue damage, morbidit y and death.